Radiotherapy, or radiation therapy, is a cancer treatment wherein ionizing radiation is used to control or kill malignant cells. Ionizing radiation works by damaging the DNA, as well as other biomolecules, of cancerous cells both directly (e.g. radiation can directly brake DNA strands) and indirectly, by generating free radicals through water radiolysis; the free radicals subsequently attacking the DNA and other biomolecules.
Radiotherapy may be curative in localized cancer or palliative for reducing pain in case of cancer spreading and metastases. It is also used before surgery to reduce the volume of the tumor and could be part of adjuvant therapy to prevent tumor recurrence after surgery. Radiation therapy is often combined with chemotherapy, with which it is synergistic.
External beam radiotherapy is the most common form of radiotherapy. It uses ionizing radiation—most often X-rays, but sometimes electron or proton beams—generated by an external source (e.g. an X-ray tube or a linear accelerator) pointed at a target region of the patient's body. In contrast to sealed source radiotherapy and unsealed source radiotherapy, in which the radiation source is inside the body, external beam radiotherapy directs the radiation at the tumor from outside the body. The energy of the ionizing radiation depends on the depth of target tumor. For X-rays it may vary from several tens of keV (kiloelectronvolts) to several MeV (megaelectronvolts).
It is known that metal (usually gold) nanoparticles localized in the target tumor may enhance the therapeutic effect of ionizing radiation. On the one hand, this is due to the fact that the metal nanoparticles enhance X-ray absorption in the tumor; on the other hand, when irradiated, they emit electrons which increase the radiolysis rate.
Nanoparticles tend to accumulate in cancer cells due to the Enhanced Permeability and Retention Effect characterizing said cells. They can also be injected into the tumor or functionalized at their surface to increase the specificity of their localization. Their size is not critical for radiotherapy; however a diameter of less than 6 nm is preferred to ease their elimination from the body.
A drawback of external beam radiotherapy is that the dose delivered to the target region of the body cannot be measured, but only be estimated a priori using physical modeling. The estimation is unavoidably affected by a significant uncertainty, which limits the scope for optimizing the therapeutic protocol.